Non‐enzymatic glycosylation of the dipeptide <scp>l</scp>‐carnosine, a potential anti‐protein‐cross‐linking agent

Hipkiss, Alan R.; Michaelis, Jfirgen; Syrris, Petros

doi:10.1016/0014-5793(95)00849-5

Cited by 204 publications

(133 citation statements)

References 21 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…In our opinion, the hypothetical role(s) of carnosine-related dipeptides could be linked to some common feature(s) concerning the metabolism of these cell populations, although no direct evidence in this direction is at present available. Nevertheless, there is strong evidence that carnosine and structurally related dipeptides possess a wide range of properties, such as antioxidant, metal chelator, free radical scavenger, inhibitor of protein glycosilation (Boldyrev et al, , 1988(Boldyrev et al, , 1997Kohen et al, 1988;Boldyrev, 1993;Hipkiss et al, 1995;Preston et al, 1998; for review, see Hipkiss, 1998), which enable them to prevent several types of damage responsible for cell senescence (McFarland and Holliday, 1994;Sri-Kantha et al, 1996). Thus, carnosine-related dipeptides could exert a protective role in cell populations of the nervous system which, due to their location and/or function and metabolism, can come in contact with potentially harmful substances.…”

Section: Discussionmentioning

confidence: 99%

“…Carnosine has been shown to act as a competitive inhibitor of non-enzymic glycosylation of proteins (Hipkiss et al, 1995). This consists of a series of posttranslational modifications in which protein amino groups and side chains react non-enzymatically with monosaccharides (forming the so called 'Amadori products'; Munch et al, 1997).…”

Section: Inhibition Of Protein Glycosylationmentioning

confidence: 99%

“…This consists of a series of posttranslational modifications in which protein amino groups and side chains react non-enzymatically with monosaccharides (forming the so called 'Amadori products'; Munch et al, 1997). The potential of carnosine to react with sugars is linked to its aminoacid sequence, which is similar to Lys-His, namely the preferred glycation sites in proteins (Shilton and Walton, 1991;Hipkiss et al, 1995). In the process of protein glycosylation, subsequent oxidations and dehydrations lead to the formation of a wide range of products referred to as advanced glycation endproducts (AGEs).…”

Section: Inhibition Of Protein Glycosylationmentioning

confidence: 99%

See 2 more Smart Citations

Carnosine-related dipeptides in the mammalian brain

Bonfanti

Peretto

Marchis

et al. 1999

Progress in Neurobiology

188

107

View full text Add to dashboard Cite

-Carnosine and structurally related dipeptides are a group of histidine-containing molecules widely distributed in vertebrate organisms and particularly abundant in muscle and nervous tissue. Although many theories have been proposed, the biological function(s) of these compounds in the nervous system remains enigmatic. The purpose of this article is to review the distribution of carnosine-related dipeptides in the mammalian brain, with particular reference to some cell populations wherein these molecules have been demonstrated to occur very recently. The high expression of carnosine in the mammalian olfactory receptor neurons led to infer that this dipeptide could play a role as a neurotransmitter/modulator in olfaction. This prediction, which has not yet been fully demonstrated, does not explain the localization of carnosine-related dipeptides in other cell types, such as glial and ependymal cells. A recent demonstration of high carnosine-like immunoreactivity in the subependymal layer of rodents, an area of the forebrain which shares with the olfactory neuroepithelium the occurrence of continuous neurogenesis during adulthood, supports the hypothesis that carnosine-related dipeptides could be implicated in some forms of structural plasticity. However, the particular distribution of these molecules in the subependymal layer, along with their expression in glial/ependymal cell populations, suggests that they are not directly linked to cell migration or cell renewal. In the absence of a unified theory about the role of carnosine-related dipeptides in the nervous system, some common features shared by different cell populations of the mammalian brain which contain these molecules are discussed.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of Protein Glycosylationmentioning

confidence: 99%

Section: Inhibition Of Protein Glycosylationmentioning

confidence: 99%

See 1 more Smart Citation

Carnosine-related dipeptides in the mammalian brain

Bonfanti

Peretto

Marchis

et al. 1999

Progress in Neurobiology

188

107

View full text Add to dashboard Cite

show abstract

“…This is the Amadori reaction that is involved in the non-enzymic glycosylation of proteins and the subsequent production, via the Maillard reaction, of advanced glycation end products (AGEs, reviewed by Monnier 1988). Carnosine reacts more strongly than lysine with various sugars and it has been suggested that its role in the cell is to act as a competitive inhibitor of non-enzymic glycosylation of proteins (Michaelis et al, 1992;Hipkiss et al, 1994Hipkiss et al, , 1995. Furthermore, it has been shown that carnosine reacts rapidly with the triose phosphate sugar intermediates of glycolysis, particularly glyceraldehyde phosphate and dihydroxyacetone phosphate (A Stevens, personal communication).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine

Holliday

McFarland²

1996

Br J Cancer

View full text Add to dashboard Cite

Summary Human diploid fibroblasts grow normally in medium containing physiological concentrations of the naturally occurring dipeptide carnosine (fi-alanyl-L-histidine). These concentrations are cytotoxic to transformed and neoplastic cells lines in modified Eagle medium (MEM), whereas these cells grow vigorously in Dulbecco's modified Eagle medium (DMEM) containing carnosine. This difference is due to The dipeptide carnosine (fl-alanyl-L-histidine) is widely distributed in mammalian tissues. It is synthesised by carnosine synthetase from its component amino acids and degraded by carnosinase. There have been many theories about its biological function, but none have been substantiated (reviewed by Quinn et al., 1992, and see Discussion). We previously showed that normal diploid human fibroblasts can grow in high concentrations of carnosine (20 mM-50 mM). Moreover, carnosine treatment can extend the lifespan of these cells and prevent the appearance of the usual signs of late-passage senescence (McFarland and Holliday, 1994). In the course of these studies we also observed that transformed rodent cell lines, such as 3T3 or CHO, were inhibited by concentrations of carnosine which did not affect diploid cells. This effect was media-dependent, in particular, it was evident that carnosine inhibition of transformed cells was clearly seen in standard MEM (minimum essential medium), but not in DMEM (Dulbecco's modification of MEM). We have followed up these preliminary studies with more detailed investigations of the effects of carnosine on transformed or tumour cell lines and have demonstrated a strong interaction between carnosine and pyruvate. In the absence of pyruvate, physiological concentrations of carnosine are cytotoxic to these cells, but cell growth is normal in medium containing both carnosine and pyruvate. We have used carnosine as a selective agent which can eliminate HeLa cells from a mixed population of these and diploid human fibroblasts. Materials and methods Cell linesThe permanent cell lines used are listed in Table I McFarland and Holliday, 1994). Cell cultureThree basic media were used: MEM, DMEM and RPMI, all from Gibco. Media were supplemented with 10% fetal calf serum (FCS), with 60 Mg ml-' penicillin and 100 jMg ml-' streptomycin. MEM was supplemented with non-essential amino acids (NEA) from Cytosystems. Dialysed FCS was prepared as follows: Spectra/Por membrane tubing (MW cutoff 6000-8000) was cut into lengths and boiled with three changes of distilled water. Aliquots of 20 ml FCS were put into each tube and dialysed overnight against 11 of Hanks' balanced salt solution at 4°C. This was repeated five times. The serum was sterilised by filtration.Cells were grown in 25 cm2 flasks or in 24-well trays and incubated at 37°C with 5% carbon dioxide. Cells were harvested with trypsin/versene (T/V), and single cell suspensions were counted with a ZF6 Coulter counter. Short-term growth experiments with HeLa cells or other cells were carried out as follows: 104 cells were inoculated into 1 ml medium ...

show abstract

“…As such, the expansion of the imidazole ring content in human skeletal muscle through an increase in the muscle carnosine concentration o ers a means to increase muscle bu ering capacity and high intensity exercise performance and capacity [1][2] . Other potential physiological roles of carnosine, such as increased calcium sensitivity [3][4] and antioxidant capacity [5][6] might also contribute to a positive e ect on exercise capacity and performance, although literature is inconclusive 7 .…”

Section: Introductionmentioning

confidence: 99%

Effect of β-alanine supplementation on 20 km cycling time trial performance

James

Cooper

Robertson

et al. 2014

Rev. bras. educ. fís. esporte

View full text Add to dashboard Cite

The effects of β-alanine supplementation on high-intensity cycling performance and capacity have been evaluated, although the effects on longer duration cycling performance are unclear. Nineteen UK category 1 male cyclists completed four 20 km cycling time trials, two before and two after supplementation with either 6.4 g•d -1 β-alanine (n = 10; BA) or a matched placebo (n = 9; P). Performance time for the 20 km time trial and 1 km split times were recorded. There was no signifi cant effect of β-alanine supplementation on 20 km time trial performance (BA-pre 1943 ± 129 s; BA-post 1950 ± 147 s; P-pre 1989 ± 106 s; P-post 1986 ± 115 s) or on the performance of each 1 km split. The effect of β-alanine on 20 km time trial performance was deemed unclear as determined by magnitude based inferences. Supplementation with 6.4 g•d -1 of β-alanine for 4 weeks did not affect 20 km cycling time trial performance in well trained male cyclists.

show abstract

Non‐enzymatic glycosylation of the dipeptide l‐carnosine, a potential anti‐protein‐cross‐linking agent

Cited by 204 publications

References 21 publications

Carnosine-related dipeptides in the mammalian brain

Carnosine-related dipeptides in the mammalian brain

Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine

Effect of β-alanine supplementation on 20 km cycling time trial performance

Contact Info

Product

Resources

About